Eosinophilic gastrointestinal diseases (EGIDs) are a spectrum of diseases characterized by eosinophilic inflammation of the gastrointestinal tract. In the past decade, there has been a dramatic increase in the incidence of EGIDs, particularly eosinophilic esophagitis (EoE). EGIDs, including eosinophilic gastroenteritis (EG) and EoE, are commonly associated with food and aeroallergen hypersensitivity. Most EGID patients have numerous food allergies, and in many patients an amino acid based elemental diet is an effective treatment. This suggests that EGID pathogenesis is due to food allergen driven eosinophilic inflammation. Omalizumab is a humanized therapeutic anti-IgE monoclonal antibody. Anti-IgE therapy reduces the concentration of circulating free IgE, blocks IgE binding to both Fc&#949;RI and CD23, and down regulates surface Fc&#949;RI on mast cells, basophils and dendritic cells. Because of the multiple actions of anti-IgE therapy that affect antigen presenting cells (APCs), it has been postulated that anti-IgE therapy may have immunomodulatory activity on T cells. We hypothesized two distinct mechanisms whereby anti-IgE therapy could inhibit allergen specific Th2 responses. First, anti-IgE down regulates Fc&#949;RI on dendritic cells and blocks CD23 mediated allergen binding to APCs, thereby inhibiting IgE facilitated Ag capture by APCs, which in turn could result in decreased allergen specific T cell activation. Second, IgE signaling of anti-IgE inhibits mast cell and basophil activation in vivo, which may decrease IL-4 and/or TSLP expression, the lack of which could inhibit Th2 cell differentiation. To test this hypothesis, we assessed anti-IgE immunomodulation of allergen specific T cell responses during the above clinical trial of omalizumab in subjects with eosinophilic gastroenteritis and food allergy. Four allergen specific T cell responses (maximal proliferation, proliferation dose response EC50, precursor frequency, and cytokine expression) were measured using carboxyfluorescein succinimidyl ester (CFSE) dye dilution and flow cytometry. There was no significant difference in allergen specific proliferation (CFSE dye dilution) between the pre-omalizumab baseline (10.0%) and the 16-week omalizumab time point (7.2%, p= 0.33). Anti-IgE therapy was associated with a small but significant left shift (opposite of the hypothesis) in the proliferative dose response to allergen, such that the EC50 at baseline was 1.5 times that of subjects on omalizumab. There was no significant difference in the precursor frequency of allergen specific T cells between the pre-omalizumab baseline (4.0 x 10e-4) and the 16 week omalizumab time point (6.5 x 10e-4, p= 0.33). No significant differences were found in the ratios of either IL-4: IFN-&#947;(baseline 0.81, omalizumab 0.63, p =0.15) or IL-5: IFN-&#947;(baseline 0.33, omalizumab 0.36, p=0.42) or of either Th2 cytokine to TNF-&#945;. In contradistinction to the hypothesis, 16 weeks of anti-IgE therapy had no effect diminishing any index of allergen specific response. In sum, we found no evidence to support the concept that anti-IgE therapy has an immunomodulatory or inhibitory effect on allergen specific Th2 cell responses. As such, these data do not support a major role for IgE mediated Ag focusing in augmenting allergen specific T cell responses in vivo. We have used similar techniques to study T cell cytokine production in mouse models of lung inflammation, using the respiratory pathogen, pneumonia virus of mice (PVM). PVM infection results in local production of the proinflammatory chemokine, CCL3, and that neutrophil recruitment in response to PVM infection is reduced dramatically in CCL3 -/- mice. In this work, we demonstrate that CCL3-mediated neutrophil recruitment is diminished in IFNgamma receptor gene-deleted mice. Similarly, in the absence of PVM infection, CCL3 overexpression alone could not elicit neutrophil recruitment in the absence of IFNgamma. These findings reveal a heretofore unrecognized interaction between the IFNgamma and CCL3, which demonstrate that IFNgamma is crucial for CCL3-mediated neutrophil recruitment in vivo.